Synthesis of amphipathic derivatives of perillyl glucoside by lipase-catalysed esterification in non conventional media

Abstract

Perillyl alcohol (POH), is a plant secondary metabolite. It is found in small concentrations in the essential oils of Chios mastic gum, lavendin, peppermint, spearmint etc. Perillyl alcohol (POH) is a monoterpene with anticarcinogenic and antitumor activity in murine tumor models and has been reported to possess chemotherapeutic activity against malignancies. Perillyl glucoside is also a natural compound contained in Perilla frutescens but no data about its biological activity have ever been reported. The studies of lipophilicity and hydrolysis in vitro of prodrugs verified that drugñ saccharide derivatives had amphipathic properties and both lipophilic and amphipathic drug derivatives had obvious controlled release characteristics. Some amphipathic macromolecule drugs are designed for improving pharmaceuticals delivery properties and generally used to enhance the permeability of cell membranes. In the present study is demonstrated the enzymatic synthesis of a perillyl glucoside fatty ester. In the first step, almond β- glucosidase catalyzed the glucosidation of perillyl alcohol by reverse hydrolysis with β-glucose in a biphasic system. In the second step, immobilised lipase from Candida antarctica (Novozym 435) was used in organic media to catalyse the acylation of perillyl glucoside with a medium chain fatty acid. The chemical structure of the products was determined by Mass Spectrometry analysis (MS). The antiproliferative activity of perillyl glucoside and perillyl glucoside fatty ester on LLC cells was investigated. Acknowledgements: This work has been funded by the project PENED 2003. The project is cofinanced 75% of public expenditure through EC - European Social Fund, 25% of public expenditure through Ministry of Development - General Secretariat of Research and Technology and through private sector, under measure 8.3 of OPERATIONAL PROGRAMME "COMPETITIVENESS" in the 3rd Community Support Programme.